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עמוד בית
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December 2018
Anca Leibovici MD, Rivka Sharon Msc and David Azoulay PhD

Background: Brain-derived neurotrophic factor (BDNF) is a neuronal growth factor that is important for the development, maintenance, and repair of the peripheral nervous system. The BDNF gene commonly carries a single nucleotide polymorphism (Val66Met-SNP), which affects the cellular distribution and activity-dependent secretion of BDNF in neuronal cells.

Objectives: To check the association between BDNF Val66Met-SNP as a predisposition that enhances the development of chemotherapy-induced peripheral neuropathy in an Israeli cohort of patients with breast cancer who were treated with paclitaxel.

Methods: Peripheral neuropathy symptoms were assessed and graded at baseline, before beginning treatment, and during the treatment protocol in 35 patients, using the reduced version of the Total Neuropathy Score (TNSr). Allelic discrimination of BDNF polymorphism was determined in the patients' peripheral blood by established polymerase chain reaction and Sanger sequencing.

Results: We found Val/Val in 20 patients (57.14%), Val/Met in 15 patients (42.86%), and Met/Met in none of the patients (0%). Baseline TNSr scores were higher in Met-BDNF patients compared to Val-BDNF patients. The maximal TNSr scores that developed during the follow-up in Met-BDNF patients were higher than in Val-BDNF patients. However, exclusion of patients with pre-existing peripheral neuropathy from the analysis resulted in equivalent maximal TNSr scores in Met-BDNF and Val-BDNF patients.

Conclusions: These observations suggest that BDNF Val66met-SNP has no detectable effect on the peripheral neuropathy that is induced by paclitaxel. The significance of BDNF Val66Met-SNP in pre-existing peripheral neuropathy-related conditions, such as diabetes, should be further investigated.

January 2000
Shoshana Merchav PhD, Ilana Tatarsky MD, Judith Chezar MD, Rivka Sharon MD, Hanna Rosenbaum MD and Yael Schechter MD

Background: The etiology of bone marrow failure, a prominent feature of paroxysmal nocturnal hemoglobulinuria, is presently unknown.

Objectives: To evaluate the possible influence of cellular immune mechanisms in the bone marrow failure of PNH.

Methods: We studied marrow erythroid colony formation in a patient with paroxysmal nocturnal hemoglobinuria without hypoplastic/aplastic marrow complications.

Results: In vitro assays revealed a pronounced inhibition of primitive erythroid (BFU-E) progenitor cell growth by marrow T lymphocytes. Removal of T cells prior to culture resulted in a 4.5-fold enhancement of BFU-E numbers. Reevaluation of in vitro erythropoiesis during steroid administration indicated a persistent, albeit less prominent, T cell inhibitory effect.

Conclusion: Our findings provide the first direct evidence for a cellular immune inhibitory phenomenon accompanying PNH.

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PNH= paroxysmal nocturnal hemoglobinuria

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